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Open Access 01-12-2022 | Thrombotic Thrombocytopenic Purpura | Research

Lombardy diagnostic and therapeutic network of thrombotic microangiopathy

Authors: I. Mancini, P. Agosti, M. Boscarino, B. Ferrari, A. Artoni, R. Palla, M. Spreafico, G. Crovetti, E. Volpato, S. Rossini, C. Novelli, S. Gattillo, L. Barcella, M. Salmoiraghi, A. Falanga, F. Peyvandi, Lombardy AREU TMA Network

Published in: Orphanet Journal of Rare Diseases | Issue 1/2022

Abstract

Background

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy (TMA) requiring urgent treatment. Standardization of its diagnosis and optimal management is challenging. This study aimed to evaluate the role of centralized, rapid testing of ADAMTS13 in patients experiencing acute TMAs requiring plasma-exchange (PEX) and to estimate the incidence of TTP in a large Italian Region.

Methods

We perfomed a cohort study in the frame of the project “Set-up of a Lombardy network for the study and treatment of patients undergoing apheresis”, including 11 transfusion centers in the Region. Consecutive patients referred from 2014 to 2016 with acute TMAs requiring PEX were enrolled. Centralized ADAMTS13 activity testing was performed at the Milan Hemophilia and Thrombosis Center within 24 h.

Results

Forty-three TMA patients (44 events) were enrolled, of whom 35 (81%) had severe ADAMTS13 deficiency. Patients with severe ADAMTS13 deficiency were younger, mainly women, with a higher prevalence of autoimmune disorders and a lower prevalence of cancer. Clinical and laboratory characteristics of patients with and without severe ADAMTS13 deficiency largely overlapped, with a lower platelet count being the only baseline marker that significantly differed between the two patient groups (ADAMTS13 activity < 10% vs ≥ 10%: median difference of -27 × 10⁹/l, 95% CI − 37 to − 3). PEX treatment was initiated in all patients, but soon discontinued in cases without severe ADAMTS13 deficiency. In this group, the mortality rate was higher and no episode exacerbations or relapses within 6 months occured. The estimated average annual incidence of acute acquired TTP events was 1.17 [0.78–1.55] per million people.

Conclusions

Severe ADAMTS13 deficiency distinguished two groups of patients with largely overlapping clinical features but different treatment and disease course. This study provides a feasible model implemented in a large Italian region for the practical clinical approach to TMAs and underlines the importance of urgent ADAMTS13 activity testing for an accurate differential diagnosis and therapeutic approach.

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Reese JA, Muthurajah DS, Kremer Hovinga JA, Vesely SK, Terrell DR, George JN. Children and adults with thrombotic thrombocytopenic purpura associated with severe, acquired Adamts13 deficiency: comparison of incidence, demographic and clinical features. Pediatr Blood Cancer. 2013;60(10):1676–82. https://doi.org/10.1002/pbc.24612.CrossRefPubMed

Terrell DR, Williams LA, Vesely SK, Lämmle B, Hovinga JA, George JN. The incidence of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: all patients, idiopathic patients, and patients with severe ADAMTS-13 deficiency. J Thromb Haemost. 2005;3(7):1432–6. https://doi.org/10.1111/j.1538-7836.2005.01436.x.CrossRefPubMed

Miesbach W, Menne J, Bommer M, et al. Incidence of acquired thrombotic thrombocytopenic purpura in Germany: a hospital level study. Orphanet J Rare Dis. 2019;14(1):260. https://doi.org/10.1186/s13023-019-1240-0.CrossRefPubMedPubMedCentral

Scully M, Yarranton H, Liesner R, et al. Regional UK TTP registry: correlation with laboratory ADAMTS 13 analysis and clinical features. Br J Haematol. 2008;142(5):819–26. https://doi.org/10.1111/j.1365-2141.2008.07276.x.CrossRefPubMed

Mariotte E, Azoulay E, Galicier L, et al. Epidemiology and pathophysiology of adulthood-onset thrombotic microangiopathy with severe ADAMTS13 deficiency (thrombotic thrombocytopenic purpura): a cross-sectional analysis of the French national registry for thrombotic microangiopathy. Lancet Haematol. 2016;3(5):e237–45. https://doi.org/10.1016/S2352-3026(16)30018-7.CrossRefPubMed

Staley EM, Cao W, Pham HP, et al. Clinical factors and biomarkers predict outcome in patients with immune-mediated thrombotic thrombocytopenic purpura. Haematologica. 2019;104(1):166–75. https://doi.org/10.3324/haematol.2018.198275.CrossRefPubMedPubMedCentral

Kremer Hovinga JA, Vesely SK, Terrell DR, Lämmle B, George JN. Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood. 2010;115(8):1500–11. https://doi.org/10.1182/blood-2009-09-243790.CrossRefPubMed

Wada H, Matsumoto T, Yamashita Y. Natural history of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Semin Thromb Hemost. 2014;40(8):866–73. https://doi.org/10.1055/s-0034-1395154.CrossRefPubMed

Lotta LA, Mariani M, Consonni D, et al. Different clinical severity of first episodes and recurrences of thrombotic thrombocytopenic purpura. Br J Haematol. 2010;151(5):488–94. https://doi.org/10.1111/j.1365-2141.2010.08385.x.CrossRefPubMed

10.

Matsumoto M, Bennett CL, Isonishi A, et al. Acquired idiopathic ADAMTS13 activity deficient thrombotic thrombocytopenic purpura in a population from Japan. PLoS One. 2012;7(3):e33029. https://doi.org/10.1371/journal.pone.0033029.CrossRefPubMedPubMedCentral

11.

Jang MJ, Chong SY, Kim IH, et al. Clinical features of severe acquired ADAMTS13 deficiency in thrombotic thrombocytopenic purpura: the Korean TTP registry experience. Int J Hematol. 2011;93(2):163–9. https://doi.org/10.1007/s12185-011-0771-5.CrossRefPubMed

12.

Blombery P, Kivivali L, Pepperell D, et al. Diagnosis and management of thrombotic thrombocytopenic purpura (TTP) in Australia: findings from the first 5 years of the Australian TTP/thrombotic microangiopathy registry. Intern Med J. 2016;46(1):71–9. https://doi.org/10.1111/imj.12935.CrossRefPubMed

13.

Benhamou Y, Boelle PY, Baudin B, et al. Cardiac troponin-I on diagnosis predicts early death and refractoriness in acquired thrombotic thrombocytopenic purpura. Experience of the French thrombotic microangiopathies reference center. J Thromb Haemost. 2015;13(2):293–302. https://doi.org/10.1111/jth.12790.CrossRefPubMed

14.

Zhou X, Ye X, Ren Y, et al. Diagnosis and management of acquired thrombotic thrombocytopenic purpura in southeast China: a single center experience of 60 cases. Front Med. 2016;10(4):430–6. https://doi.org/10.1007/s11684-016-0492-5.CrossRefPubMed

15.

Zafrani L, Mariotte E, Darmon M, et al. Acute renal failure is prevalent in patients with thrombotic thrombocytopenic purpura associated with low plasma ADAMTS13 activity. J Thromb Haemost. 2015;13(3):380–9. https://doi.org/10.1111/jth.12826.CrossRefPubMed

16.

Page EE, Kremer Hovinga JA, Terrell DR, Vesely SK, George JN. Thrombotic thrombocytopenic purpura: diagnostic criteria, clinical features, and long-term outcomes from 1995 through 2015. Blood Adv. 2017;1(10):590–600. https://doi.org/10.1182/bloodadvances.2017005124.CrossRefPubMedPubMedCentral

17.

Brazelton J, Oster RA, McCleskey B, Fuller J, Adamski J, Marques MB. Increased troponin I is associated with fatal outcome in acquired thrombotic thrombocytopenic purpura. J Clin Apher. 2017;32(5):311–8. https://doi.org/10.1002/jca.21510.CrossRefPubMed

18.

Scully M, Cataland S, Coppo P, et al. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost. 2017;15(2):312–22. https://doi.org/10.1111/jth.13571.CrossRefPubMed

19.

Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020;18(10):2486–95. https://doi.org/10.1111/jth.15006.CrossRefPubMedPubMedCentral

20.

Piedrafita A, Ribes D, Cointault O, Chauveau D, Faguer S, Huart A. Plasma exchange and thrombotic microangiopathies: from pathophysiology to clinical practice. Transfus Apher Sci. 2020;59(6):102990. https://doi.org/10.1016/j.transci.2020.102990.CrossRefPubMed

21.

Mackie I, Mancini I, Muia J, et al. International council for standardization in haematology (ICSH) recommendations for laboratory measurement of ADAMTS13. Int J Lab Hematol. 2020;42(6):685–96. https://doi.org/10.1111/ijlh.13295.CrossRefPubMed

22.

Schwartz J, Padmanabhan A, Aqui N, et al. Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the writing committee of the american society for apheresis. The seventh special issue. J Clin Apher. 2016;31(3):149–62. https://doi.org/10.1002/jca.21470.CrossRefPubMed

23.

Coppo P, Schwarzinger M, Buffet M, et al. Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center experience. PLoS ONE. 2010;5(4):e10208. https://doi.org/10.1371/journal.pone.0010208.CrossRefPubMedPubMedCentral

24.

Bendapudi PK, Li A, Hamdan A, et al. Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative. Br J Haematol. 2015;171(5):836–44. https://doi.org/10.1111/bjh.13658.CrossRefPubMed

25.

Bendapudi PK, Hurwitz S, Fry A, et al. Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study. Lancet Haematol. 2017;4(4):e157–64. https://doi.org/10.1016/S2352-3026(17)30026-1.CrossRefPubMed

26.

Paydary K, Banwell E, Tong J, Chen Y, Cuker A. Diagnostic accuracy of the PLASMIC score in patients with suspected thrombotic thrombocytopenic purpura: a systematic review and meta-analysis. Transfusion. 2020;60(9):2047–57.PubMed

27.

Kim CH, Simmons SC, Wattar SF, Azad A, Pham HP. Potential impact of a delayed ADAMTS13 result in the treatment of thrombotic microangiopathy: an economic analysis. Vox Sang. 2020;115(5):433–42. https://doi.org/10.1111/vox.12912.CrossRefPubMed

28.

Veyradier A, editor PTT. épidémiologie de la cohorte du CNR-MAT sur 16 ans. Compte rendu de la 8è réunion du CNR-MAT; 2015 10/16/2015; Paris2015.

Title: Lombardy diagnostic and therapeutic network of thrombotic microangiopathy
Authors: I. Mancini
P. Agosti
M. Boscarino
B. Ferrari
A. Artoni
R. Palla
M. Spreafico
G. Crovetti
E. Volpato
S. Rossini
C. Novelli
S. Gattillo
L. Barcella
M. Salmoiraghi
A. Falanga
F. Peyvandi
Lombardy AREU TMA Network
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Thrombotic Thrombocytopenic Purpura
Thrombotic Microangiopathy
Published in: Orphanet Journal of Rare Diseases / Issue 1/2022
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-022-02400-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Lombardy diagnostic and therapeutic network of thrombotic microangiopathy

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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